Amino acid decarboxylases specificity

Manometric determiaation of L-lysiae, L-argioine, L-leuciae, L-ornithine, L-tyrosiae, L-histidine, L-glutamic acid, and L-aspartic acid has been reviewed (136). This method depends on the measurement of the carbon dioxide released by the T.-amino acid decarboxylase which is specific to each amino acid. 

Decarboxylation of histidine to histamine is catalyzed by a broad-specificity aromatic L-amino acid decarboxylase that also catalyzes the decarboxylation of dopa, 5-hy-droxytryptophan, phenylalanine, tyrosine, and tryptophan. a-Methyl amino acids, which inhibit decarboxylase activity, find appfication as antihypertensive agents. Histidine compounds present in the human body include ergothioneine, carnosine, and dietary anserine (Figure 31-2). Urinary levels of 3-methylhistidine are unusually low in patients with Wilson s disease. 

By contrast, the cytoplasmic decarboxylation of dopa to dopamine by the enzyme dopa decarboxylase is about 100 times more rapid (Am 4x 10 " M) than its synthesis and indeed it is difficult to detect endogenous dopa in the CNS. This enzyme, which requires pyridoxal phosphate (vitamin B6) as co-factor, can decarboxylate other amino acids (e.g. tryptophan and tyrosine) and in view of its low substrate specificity is known as a general L-aromatic amino-acid decarboxylase. 

Histamine is synthesised by decarboxylation of histidine, its amino-acid precursor, by the specific enzyme histidine decarboxylase, which like glutaminic acid decarboxylase requires pyridoxal phosphate as co-factor. Histidine is a poor substrate for the L-amino-acid decarboxylase responsible for DA and NA synthesis. The synthesis of histamine in the brain can be increased by the administration of histidine, so its decarboxylase is presumably not saturated normally, but it can be inhibited by a fluoromethylhistidine. No high-affinity neuronal uptake has been demonstrated for histamine although after initial metabolism by histamine A-methyl transferase to 3-methylhistamine, it is deaminated by intraneuronal MAOb to 3-methylimidazole acetic acid (Fig. 13.4). A Ca +-dependent KCl-induced release of histamine has been demonstrated by microdialysis in the rat hypothalamus (Russell et al. 1990) but its overflow in some areas, such as the striatum, is neither increased by KCl nor reduced by tetradotoxin and probably comes from mast cells. 

Ichinose, H., Sumi-Ichinose, C., Ohye, T., Hagino, Y., Fujita, K., and Nagatsu, T. (1992). Tissue-specific alternative splicing of the 1st exon generates 2 types of messenger-RNAs in human aromatic L-amino acid decarboxylase. Biochemistry 31 11546— 11550. 

Thai, A. L. V., Coste, E., Allen, J. M., Palmiter, R. D., and Weber, M. J. (1993). Identification of a neuron-specific promoter of human aromatic L-amino acid decarboxylase gene. Mol. Brain. Res 17 227-238. 

A group of enzymes which may be employed in the measurement of L amino acids are the L-amino acid decarboxylases (EC 4.1.1) of bacterial origin, many of which are substrate specific. They catalyse reactions of the type ... 

Drugs have been developed which specifically inhibit the L-aromatic amino acid decarboxylase step in catecholamine synthesis and thereby lead to a reduction in catecholamine concentration. Carbidopa and benserazide are examples of decarboxylase inhibitors which are used clinically to... 

Dopamine is the decarboxylation product of DOPA, dihydroxyphenylalanine, and is formed in a reaction catalysed by DOPA decarboxylase. This enzyme is sometimes referred to as aromatic amino acid decarboxylase, since it is relatively non-specific in its action and can catalyse decarboxylation of other aromatic amino acids, e.g. tryptophan and histidine. DOPA is itself derived by aromatic hydroxylation of tyrosine, using tetrahydrobiopterin (a pteridine derivative see Section 11.9.2) as cofactor. 

The neurotransmitter 5-hydroxytryptamine (5-HT, serotonin) is formed from tryptophan by hydroxylation then decarboxylation, paralleling the tyrosine — dopamine pathway. The non-specific enzyme aromatic amino acid decarboxylase again catalyses the decarboxylation. 

That amines formed from naturally occurring amino acids are partly responsible for chronic hypertension is a rather attractive hypothesis first suggested by the experiments of Holtz (35). Besides the normal metabolic enzymes of amino acids, tissues, especially kidney, liver, and brain, contain amino acid decarboxylases, some of them specific for certain amino acids, some less so. These are anaerobic enzymes. After decarboxylation, certain monoamines are deaminated by amine oxidases which are sensitive to oxygen tension. The best known of these oxidases is the enzyme of Blaschko, Richter, and Schlossmann (9), which may be a mixture of three or more (29), and which is specific for many nonsubstituted vasoactive amines found in the body, with the notable exception of histamine. 

A number of decarboxylase enzymes have been described as catalysts for the preparation of chiral synthons, which are difficult to access chemically (see Chapter 2).264 The amino acid decarboxylases catalyze the pyridoxal phosphate (PLP)-dependent removal of C02 from their respective substrates. This reaction has found great industrial utility with one specific enzyme in particular, L-aspartate-P-decarboxylase (E.C. 4.1.1.12) from Pseudomonas dacunhae. This biocatalyst, most often used in immobilized whole cells, has been utilized by Tanabe to synthesize L-alanine on an industrial scale (multi-tons) since the mid-1960s (Scheme 19.33).242-265 Another use for this biocatalyst has been the resolution of racemic aspartic acid to produce L-alanine and D-aspartic acid (Scheme 19.34). The cloning of the L-aspartate-P-decarboxylase from Alcaligenes faecalis into E. coli offers additional potential to produce both of these amino acids.266... 

Numerous other amino acid decarboxylases have been isolated and characterized, and much interest has been shown as a result of the irreversible nature of the reaction with the release of C02 as the thermodynamic driving force. Although these enzymes have narrow substrate-specificity profiles, their utility has been widely demonstrated. Additional industrial processes will continue to be developed once other decarboxylases become available. Such biocatalysts would include the aromatic amino acid (E.C. 4.1.1.28), phenylalanine (E.C. 4.1.1.53) and tyrosine (E.C. 4.1.1.25) decarboxylases, which likely could be used to produce derivatives of their respective substrates. These derivatives are finding increased use in the development of peptidomimetic drugs and as possible positron emission tomography imaging agents.267-268... 

Specific L-amino acid decarboxylases, produced by certain bacteria under selected growth conditions, catalyze the decarboxylation of certain amino acids (Ref. 54, Equation 16). 

Studies on Bacterial Amino-acid Decarboxylases. 5. The Use of Specific... 

Synthesis and metabolism of catecholamines. Arrows indicate molecular conversions catalyzed by specific enzymes. Bold arrows indicate major (preferred) pathways. Enzymes (I) tyrosine hydroxylase (2) aromatic L-amino acid decarboxylase (3) dopamine-jSymonooxygenase (4) PNMT (5) cateckel-o-methyltransferase (6) monoamine oxidase. 

Maintenance of HT (and norepinephrine also) in the rat brain is dependent upon the integrity of the medial forebrain bundle within the lateral hypothalamus When the medial forebrain bundle degenerates as a consequence of a lesion produced in the lateral hypothalamus, HT is depleted in the telencephalon ipsilateral to the lesion in the rat and cat. Concomitant with depletion of HT in this region is a decrease in the activity of L-aromatic amino acid decarboxylase, the enzyme that forms HT from its precursor Specific lesions can selectively affect monoamine levels lesions in the central gray area and the septum lower the level of HT in the telencephalon without affecting the level of... 

A number of amines derived from aromatic amino acid are present in brain in trace quantities. Since aromatic L-amino acid decarboxylase shows a broad substrate specificity, it is not surprising that compounds such as tyramine, tryptamine, phenylethylamine, and histamine are present in brain. These amines are derived from the simple decarboxylation of the corresponding... 

Thus there is much evidence to suggest that the histidine decarboxylase having its maximum activity in the pH range 8-0-9-5 is a single enzyme which can decarboxylate not only L-histidine, but also L-/S-(3,4-dihydroxyphenyl)-alanine and L-5-hydroxytryptophan. Enzyme preparations which decarboxylate one or more of these three compounds have been found also to decarboxylate the substances listed in Table 4.3, thus providing support for the existence of a general aromatic amino acid decarboxylase. It is this enzyme which will be referred to as the non-specific histidine decarboxylase. 

In some instances the results obtained by different groups of workers have been sufficiently at variance, particularly where weak substrates have been studied, for doubt to be cast on the existence of a general aromatic amino acid decarboxylase. Thus it has been claimed that some preparations which contain DOPA and 5-HTP decarboxylase activities do not decarboxylate histidine - . In these instances, the sensitivity or specificity of the analytical procedures are open to doubt, and the results require confirmation. In view of conflicting reports in the literature, further experiments should also be carried out to determine whether the mono- and dihydroxyphenylserines > are indeed substrates of non-specific histidine decarboxylase. The status of /)-tyrosine also requires clarification formerly it was not considered to be a substrate " , but recent evidence suggests that it may, in fact, be decarboxylated . 

The function of the non-specific histidine decarboxylase of rabbit- or guinea-pig liver and kidney remains to be clarified. However, in view of its wide substrate specificity [Table 4.3), this enzyme may rather be a general aromatic L-amino acid decarboxylase, the purpose of which is to produce other physiologically important amines in addition to histamine. 

The synthesis of serotonin from tryptophan is carried out in two steps controlled by two enzymes tryptophan hydroxylase (TPH) and aromatic L-amino acid decarboxylase (AADC). The second enzyme, A ADC, is also known as DOPA carboxylase or 5-hydroxytryptophan carboxylase when it acts specifically in 5-HT synthesis. In the first step, the TPH adds a hydroxyl chemical group (OH) to tryptophan to make 5-hydroxytryptophan, Fig (1). In the second step, AADC removes the carboxyl group (-COOH) from 5-hydroxy tryptophan to make serotonin. Fig (2). 

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